Polymeric microneedle technologies for minimally invasive biomarker monitoring and drug delivery Hannah Leese 1 , Joseph G. Turner 1,2 Antonios Keirouz 1,2 , Yasemin L. Mustafa 1,2 , Emily Lay 3,4 , Shuxian Li 3 , Ute Jungwirth 2,4 , Frank Marken 5 , Maisem Laabei 3 , Pedro Estrela 2,6 1 University of Bath, UK, 2 Centre for Biosensors, Bioelectronics and Biodevices, University of Bath, UK, 3 Department of Life Sciences, University of Bath, UK, 4 Centre for Therapeutic Innovation, University of Bath, UK, 5 Department of Chemistry, University of Bath, UK, 6 Department of Electronic and Electrical Engineering, University of Bath, UK Polymeric-microneedle technologies as biointerface materials show promise for the minimally invasive monitoring of bioanalytes and transdermal delivery of therapeutics. The interstitial fluid (ISF) is an emerging source of biomarkers for detection, as well as providing a pathway for transdermal drug delivery, where minimally invasive devices can penetrate skin (without pain). Microneedles (MNs) are placed in an array andused to pierce through the outermost skin layer,(Stratum Corneum). Traditionally, MNs have beenmade from solidmetal or ceramics, making fabricationmore challenging and costly. More recently,alternative MNs have been utilised for various applications and made from several biomaterialsincluding polymers. 1 We have developed a range of polymeric microneedles including hydrogel-forming microneedles (HFMs), 3D-printed hollow microneedle (HMNs) devices and conductive polymeric solid microneedle (CP-MNs) arrays as biointerface materials. Desktop 3D-printingmedical deviceshas many benefits, enabling rapid and low-cost production, allowing for accelerated product development and tailored/personalised design. Here,alow force stereolithography3D- printing methodwas utilisedfor the direct production of HMNs. These HMNspenetrate ex vivo skin,extract fluidand when altering the surface chemistry for increased hydrophilicity, aids passive fluid flow for the detection of analytes without any external pumps. The printing methodology was also used in amicro-moulding process to formnegative moulds for HFM formation and drug encapsulation. Using amoxicillin as a model drug,the controlled release was observedover therapeutically relevant timescales by altering the loaded drug concentration and hydrogel crosslinking density. Furthermore, we reportthe fabrication of conductive microneedle (CP-MNs) arrays. 2 These entirely polymer-based solid microneedle arrays perform as dry conductive electrodes, whilst omitting the requirement of a metallic seed layer. The microneedle arrays penetrate ex vivo porcine skin grafts without compromising conductivity or microneedle morphology and demonstrate coating durability over multiple penetration cycles. 2 The non-cytotoxic nature of the CP-MNs was also evaluated using human fibroblast cells. These proposed microneedle fabrication strategies offer compelling approaches to manufacturing polymer-based microneedle devices asminimally invasive biodevices and wearables. Acknowledgements: This research was financially supported by the Engineering and Physical Sciences Research Council Grant EP/V010859/1 and the Royal Society Research Grant RSG\R1\201185. References 1. Turner, J. G., White, L. R., Estrela, P., Leese, H. S., Hydrogel-Forming Microneedles: Current Advancements and Future Trends. Macromol. Biosci. 2021, 21, 2000307. 2. Keirouz, A., Mustafa, Y.L., Turner, J.G., Lay, E., Jungwirth, U., Marken, F. and Leese, H.S., 2022. Conductive Polymer- Coated 3D Printed Microneedles: Biocompatible Platforms for Minimally Invasive Biosensing Interfaces. Small , p.2206301
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